Lipid metabolic dysregulation in diabetic kidney disease: mechanisms, cellular impact, and therapeutic strategies

Diabetic kidney disease (DKD) represents a prevalent and severe complication of diabetes mellitus, with growing evidence highlighting the critical role of lipid metabolic dysregulation in its pathogenesis. This review systematically examines the complex interplay between aberrant lipid metabolism and DKD progression, focusing on three major pathways: fatty acid metabolism disturbances, cholesterol homeostasis imbalance, and sphingolipid signaling alterations. We detail how these metabolic perturbations contribute to renal cell injury through multiple mechanisms, including in podocytes, tubular epithelial cells, and mesangial cells. Emerging therapeutic strategies targeting these metabolic pathways are comprehensively evaluated. Special emphasis is placed on recent advances in understanding cell-specific lipid metabolic reprogramming and its clinical implications. The review also discusses current challenges in translating these findings into clinical practice and proposes future research directions for developing personalized therapeutic approaches based on lipid metabolic profiling in DKD patients.